Characterization of inflammatory response in hepatorenal syndrome: Relationship with kidney outcome and survival

Background Several lines of evidence indicate that decompensated cirrhosis is characterized by the presence of systemic inflammation. Hepatorenal syndrome (HRS-AKI) is a unique type of renal failure that occurs at late stages of cirrhosis. However, confirmation of the presence and significance of such inflammatory response in HRS-AKI is lacking. Aim and Methods To characterize the systemic inflammatory response, as estimated by measuring a large number of cytokines, in 161 patients hospitalized for an acute decompensation of cirrhosis: 44 patients without acute kidney injury (AKI), 63 patients with hypovolaemia-induced AKI and 58 patients with HRS-AKI. Results HRS-AKI was characterized by an altered cytokine profile compared to the other two groups, particularly IL-6, IL-8, TNF-alpha, VCAM-1, fractalkine and MIP-1 alpha. The inflammatory response was not related to presence of bacterial infection, concomitant acute-on-chronic liver failure or severity of renal dysfunction. Patients who responded to terlipressin and albumin had only a decrease in TNF-alpha and RANTES after treatment without changes in other cytokines. Interestingly, patients with persistent HRS-AKI had higher levels of IP-10 and VCAM-1 compared to those with resolution of HRS-AKI. VCAM-1 was also an independent predictor of 3-month mortality. A systems biology analysis approach showed that the inflammatory status of HRS-AKI was similar to that of chronic nonhepatic inflammatory conditions, such as lupus erythematosus or inflammatory bowel disease. Conclusion Hepatorenal syndrome is characterized by a marked systemic inflammatory state, reminiscent of that of nonhepatic inflammatory diseases, that correlates with patient outcomes.